Our goal is to kill tumor cells selectively by treating tumor-bearing hosts with potent cytotoxins conjugated to tumor-specific antibodies. We have already shown that diphtheria toxin conjugated to antibodies against cell-surface antigens can kill selectively cells which bear those antigens. Such antibody-toxin conjugates exert antitumor effects in vivo when prepared with antibodies directed against tumor-specific antigens. To date, however, their therapeutic usefulness against experimental tumors has been limited by their content of toxic but immunologically non-specific impurities. We now plan to try to improve the therapeutic efficacy of this approach to the point where treatment with conjugates induces regressions of established tumors, using the following methods: 1. Improved purification of conjugates utilizing immunoadsorbent techniques. 2. Combined chemo-immunotherapy. 3. Utilization of chemically modified or of mutant diphtheria toxins known to have reduced binding affinity for cells, to minimize the non-specific toxicity of conjugates. 4. Preparation and evaluation of conjugates between antibodies and cytotoxic agents other than diphtheria toxin. These include ricin, phospholipase C, and pancreatic ribonuclease. If these studies succeed in enhancing the therapeutic efficacy of antibody-toxin conjugates, arrangement necessary for conducting therapeutic trials in cancer patients will be initiated.